RETRACTED: PNU‐74654 enhances the antiproliferative effects of 5‐FU in breast cancer and antagonizes thrombin‐induced cell growth via the Wnt pathway

Rahmani, Farzad; Amerizadeh, Forouzan; Hassanian, Seyed Mahdi; Hashemzehi, Milad; Nasiri, Seyedeh-Najibeh; Fiuji, Hamid; Ferns, Gordon A.; Khazaei, Majid; Rezayi, Majid

doi:10.1002/jcp.28104

Cited by 24 publications

(21 citation statements)

References 38 publications

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“…This result is well explained by the process of Wnt/β-catenin signaling. In a breast cancer model, PNU-74654, either alone or in combination with fluorouracil (5-FU), was shown to suppress breast cancer cell growth and to synergistically enhance the antiproliferative activity of gemcitabine [32]. The PNU-74654/5-FU combination increased the percentage of cells in the S-phase and significantly induced apoptosis in PNU-7465-treated breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…PNU-74654 has been shown to significantly decrease cell proliferation, increase tumor cell apoptosis, decrease nuclear β-catenin accumulation and impair CTNNB1/β-catenin expression in adrenocortical tumors [31]. PNU-74654 has also shown antitumor efficacy in breast cancers, where it causes tumor shrinkage and increased tumor cell apoptosis [32]. To our knowledge, no study has yet explored the potential for using PNU-74654 as a treatment in TC.…”

Section: Introductionmentioning

confidence: 99%

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PNU-74654 Suppresses TNFR1/IKB Alpha/p65 Signaling and Induces Cell Death in Testicular Cancer

Chen¹,

Sung²,

Yu³

et al. 2022

CIMB

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Testicular cancer (TC) is a rare malignancy worldwide and is the most common malignancy in males aged 15–44 years. The Wnt/β-catenin signaling pathway mediates numerous essential cellular functions and has potentially important effects on tumorigenesis and cancer progression. The search for drugs to inhibit this pathway has identified a small molecule, PNU-74654, as an inhibitor of the β-catenin/TCF4 interaction. We evaluated the therapeutic role of PNU-74654 in two TC cell lines, NCCIT and NTERA2, by measuring cell viability, cell cycle transition and cell death. Potential pathways were evaluated by protein arrays and Western blots. PNU-74654 decreased cell viability and induced apoptosis of TC cells, with significant increases in the sub G1, Hoechst-stained, Annexin V-PI-positive rates. PNU-74654 treatment of both TC cell lines inhibited the TNFR1/IKB alpha/p65 pathway and the execution phase of apoptosis. Our findings demonstrate that PNU-74654 can induce apoptosis in TC cells through mechanisms involving the execution phase of apoptosis and inhibition of TNFR1/IKB alpha/p65 signaling. Therefore, small molecules such as PNU-74654 may identify potential new treatment strategies for TC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

PNU-74654 Suppresses TNFR1/IKB Alpha/p65 Signaling and Induces Cell Death in Testicular Cancer

Chen¹,

Sung²,

Yu³

et al. 2022

CIMB

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show abstract

“…Importantly, it is involved in self-renewal of healthy stem cells (Majidinia, Aghazadeh, Jahanban-Esfahlani, & Yousefi, 2018;Uribe-Etxebarria, Agliano, Unda, & Ibarretxe, 2019) as well as of both solid cancer (Najafi, Farhood, & Mortezaee, 2019) and leukemia stem cells (LSCs) (Lento, Congdon, Voermans, Kritzik, & Reya, 2013). An aberrant increase in the levels of β-catenin exerts oncogenic effects via the activation of downstream gene expression programs in colorectal cancer (Morin et al, 1997;Rahmani, Avan, Hashemy, & Hassanian, 2018;Vermeulen et al, 2010), endometrial cancer (Giannakis et al, 2014;Liu, Chang, Lu, & Xiang, 2019), breast cancer (Gao et al, 2019;Khramtsov et al, 2010;Mohammadi-Yeganeh, Hosseini, & Paryan, 2019;Rahmani et al, 2019), prostate cancer (Pashirzad et al, 2019), bladder cancer (Xie et al, 2019), lung cancer (Wang, Zhou, Xu, & Hu, 2018b), glioblastoma (He et al, 2019) as well as in blood malignancies (Staal & Sen, 2008;Zhao et al, 2007). More specifically, ≥85% of pediatric T-ALL patients display increased β-catenin expression and upregulation of the Wnt target genes AXIN2, C-MYC, TCFL, and LEF (Arensman et al, 2014;Fernandes et al, 2017;Ng et al, 2014).…”

mentioning

confidence: 99%

Targeting Wnt/β‐catenin and PI3K/Akt/mTOR pathways in T‐cell acute lymphoblastic leukemia

Evangelisti

Chiarini

Cappellini

et al. 2020

Journal Cellular Physiology

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T‐cell acute lymphoblastic leukemia (T‐ALL) is an aggressive hematological disorder that results from the clonal transformation of T‐cell precursors. Phosphatidylinositol 3‐kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) and canonical Wnt/β‐catenin signaling pathways play a crucial role in T‐cell development and in self‐renewal of healthy and leukemic stem cells. Notably, β‐catenin is a transcriptional regulator of several genes involved in cancer cell proliferation and survival. In this way, aberrations of components belonging to the aforementioned networks contribute to T‐ALL pathogenesis. For this reason, inhibition of both pathways could represent an innovative strategy in this hematological malignancy. Here, we show that combined targeting of Wnt/β‐catenin pathway through ICG‐001, a CBP/β‐catenin transcription inhibitor, and of the PI3K/Akt/mTOR axis through ZSTK‐474, a PI3K inhibitor, downregulated proliferation, survival, and clonogenic activity of T‐ALL cells. ICG‐001 and ZSTK‐474 displayed cytotoxic effects, and, when combined together, induced a significant increase in apoptotic cells. This induction of apoptosis was associated with the downregulation of Wnt/β‐catenin and PI3K/Akt/mTOR pathways. All these findings were confirmed under hypoxic conditions that mimic the bone marrow niche where leukemic stem cells are believed to reside. Taken together, our findings highlight potentially promising treatment consisting of cotargeting Wnt/β‐catenin and PI3K/Akt/mTOR pathways in T‐ALL settings.

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“…The hallmark changes of eMT include a reduction in intercellular adhesion and a loss of cell polarity (55). it is well established that the Wnt signaling pathway can induce eMT, which subsequently leads to cell invasion and migration (56,57), and a number of previous studies demonstrated that the Wnt/β-catenin signaling pathway promotes breast cancer progression (58)(59)(60). The Wnt signaling pathway is composed of two different intracellular signaling pathways, the canonical and non-canonical pathway (61)(62)(63).…”

Section: Discussionmentioning

confidence: 99%

Astragalus polysaccharide inhibits breast cancer cell migration and invasion by regulating epithelial‑mesenchymal transition via the Wnt/β‑catenin signaling pathway

Yang

Sun

et al. 2020

Mol Med Report

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epithelial-mesenchymal transition (eMT) serves an important role in tumor migration and invasion. Astragalus polysaccharide (aPS), which is the main component of the traditional chinese medicine Astragalus membranaceus, has been identified to display an antitumor effect. However, the effects and mechanisms of aPS during breast cancer migration and invasion are not completely understood. The present study investigated whether aPS inhibited breast cancer migration and invasion by modulating the eMT pathway. an MTT assay and a Ki67 immunofluorescence staining assay demonstrated that aPS inhibited the proliferation of breast cancer cells. The results of the wound healing and Transwell Matrigel invasion assays suggested that aPS decreased the migration and invasion of breast cancer cells. The western blotting and immunofluorescence analyses further demonstrated that aPS had a regulatory effect on eMT-related molecules. aPS decreased the expression levels of Snail and vimentin, but increased e-cadherin expression. aPS also downregulated Wnt1, β-catenin and downstream target expression. additionally, the present results suggested that aPS decreased the proliferation, and eMT-mediated migration and invasion of cells by inhibiting the Wnt/β-catenin signaling pathway. The present study suggested that aPS may serve as a promising therapeutic agent for breast cancer.

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RETRACTED: PNU‐74654 enhances the antiproliferative effects of 5‐FU in breast cancer and antagonizes thrombin‐induced cell growth via the Wnt pathway

Cited by 24 publications

References 38 publications

PNU-74654 Suppresses TNFR1/IKB Alpha/p65 Signaling and Induces Cell Death in Testicular Cancer

PNU-74654 Suppresses TNFR1/IKB Alpha/p65 Signaling and Induces Cell Death in Testicular Cancer

Targeting Wnt/β‐catenin and PI3K/Akt/mTOR pathways in T‐cell acute lymphoblastic leukemia

Astragalus polysaccharide inhibits breast cancer cell migration and invasion by regulating epithelial‑mesenchymal transition via the Wnt/β‑catenin signaling pathway

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